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Regulatory T cells function at the early stage of tumor progression in a mouse model of tongue squamous cell carcinoma

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Abstract

The objective of this study was to observe the distribution of regulatory T cells (Tregs) in the development of tongue squamous cell carcinoma (SCC) and to determine the role of Tregs in the progression of tongue SCC. A mouse model of 4-nitroquinoline-1-oxide (4NQO)-induced-tongue SCC was established. The expression of Forkhead box P3 (Foxp3), interleukin 10, transforming growth factor-β, chemokine CC motif ligands 17, 20, and CC chemokine receptor 4 was determined using real-time quantitative polymerase chain reaction. Foxp3 expression was also analyzed using immunohistochemistry. The results were compared with those of control mice and of 4NQO-treated mice treated with a cyclooxygenase-2 (COX-2) inhibitor. Well to moderately differentiated tongue SCC was induced in all of the experimental mice. The amount of Tregs of the experimental mice was over 10 times as much as control mice at the early stage of tumor progression. COX-2 inhibitor did not prevent the progression of tongue SCC and did not reduce the total amount of Tregs. Tregs function at the early stage of the development of tongue SCC, and it may be effective to suppress Tregs at the early stage of tumor progression for the treatment and/or prevention of tongue SCC.

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Abbreviations

4NQO:

4-nitroquinoline-1-oxide

CCL:

Chemokine CC motif ligand(s)

CCR:

CC chemokine receptor

CI:

Confidence interval(s)

PG:

Prostaglandin

PGE2:

Prostaglandin E2

RT-PCR:

Real-time quantitative polymerase chain reaction

SCC:

Squamous cell carcinoma

Th3:

T helper 3

Tr1(17):

Type 1(17) T regulatory

Tregs:

Regulatory T cells

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Acknowledgments

This work was supported by a Grant-in-Aid for Scientific Research C from the Ministry of Education, Culture, Sports, Science and Technology, Japan [Grant No. 25462684 to Orita Y ] and by Wesco Scientific Promotion Foundation [to Orita Y].

Author information

Authors and Affiliations

  1. Department of Otolaryngology, Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan

    Kentaro Miki, Yorihisa Orita & Kazunori Nishizaki

  2. Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan

    Yuka Gion, Kyotaro Ohno, Mai Takeuchi, Tadashi Yoshino & Yasuharu Sato

  3. Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan

    Soshi Takao

  4. Department of Immunology, Nara Medical University, Nara, Japan

    Toshihiro Ito

  5. Department of Head and Neck, Shikoku Cancer Center, Ehime, Japan

    Hiroyuki Hanakawa

  6. Department of Otolaryngology, Head and Neck Surgery, Himeji Red Cross Hospital, Hyogo, Japan

    Tomoyasu Tachibana & Takuma Makino

  7. Department of Otolaryngology Head and Neck Surgery, National Hospital Organization Okayama Medical Center, Okayama, Japan

    Hidenori Marunaka

  8. Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Tokyo, Japan

    Akira Minoura

  9. Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan

    Akihiro Matsukawa

  10. Division of Pathophysiology, Okayama University Graduate School of Health Sciences, Okayama, Japan

    Yasuharu Sato

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  1. Kentaro Miki
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  2. Yorihisa Orita
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  3. Yuka Gion
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Correspondence to Yorihisa Orita.

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Miki, K., Orita, Y., Gion, Y. et al. Regulatory T cells function at the early stage of tumor progression in a mouse model of tongue squamous cell carcinoma. Cancer Immunol Immunother 65, 1401–1410 (2016). https://doi.org/10.1007/s00262-016-1902-x

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  • DOI: https://doi.org/10.1007/s00262-016-1902-x

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